全文获取类型
收费全文 | 5087篇 |
免费 | 417篇 |
国内免费 | 245篇 |
专业分类
耳鼻咽喉 | 36篇 |
儿科学 | 68篇 |
妇产科学 | 68篇 |
基础医学 | 911篇 |
口腔科学 | 172篇 |
临床医学 | 337篇 |
内科学 | 629篇 |
皮肤病学 | 112篇 |
神经病学 | 325篇 |
特种医学 | 173篇 |
外国民族医学 | 1篇 |
外科学 | 265篇 |
综合类 | 756篇 |
现状与发展 | 1篇 |
预防医学 | 452篇 |
眼科学 | 67篇 |
药学 | 603篇 |
1篇 | |
中国医学 | 245篇 |
肿瘤学 | 527篇 |
出版年
2024年 | 14篇 |
2023年 | 74篇 |
2022年 | 121篇 |
2021年 | 286篇 |
2020年 | 166篇 |
2019年 | 190篇 |
2018年 | 161篇 |
2017年 | 152篇 |
2016年 | 164篇 |
2015年 | 152篇 |
2014年 | 283篇 |
2013年 | 320篇 |
2012年 | 232篇 |
2011年 | 239篇 |
2010年 | 202篇 |
2009年 | 220篇 |
2008年 | 233篇 |
2007年 | 238篇 |
2006年 | 226篇 |
2005年 | 176篇 |
2004年 | 133篇 |
2003年 | 163篇 |
2002年 | 139篇 |
2001年 | 127篇 |
2000年 | 108篇 |
1999年 | 86篇 |
1998年 | 88篇 |
1997年 | 97篇 |
1996年 | 96篇 |
1995年 | 72篇 |
1994年 | 84篇 |
1993年 | 65篇 |
1992年 | 57篇 |
1991年 | 58篇 |
1990年 | 52篇 |
1989年 | 71篇 |
1988年 | 53篇 |
1987年 | 49篇 |
1986年 | 54篇 |
1985年 | 53篇 |
1984年 | 27篇 |
1983年 | 20篇 |
1982年 | 33篇 |
1981年 | 23篇 |
1980年 | 23篇 |
1979年 | 17篇 |
1978年 | 13篇 |
1977年 | 14篇 |
1976年 | 9篇 |
1974年 | 4篇 |
排序方式: 共有5749条查询结果,搜索用时 171 毫秒
41.
Cloning of the nitrate reductase gene of Stagonospora (Septoria) nodorum and its use as a selectable marker for targeted transformation 总被引:1,自引:0,他引:1
The nitrate reductase gene (NIA1) of the phytopathogenic fungus Stagonospora (Septoria) nodorum has been cloned from a cosmid library by homologous hybridisation with a PCR-generated probe. A 6.7-kb fragment carrying
the NIA1 gene was subcloned and partially characterised by restriction mapping. Sequencing of the gene indicated a high degree of
homology, both at the nucleotide and amino-acid levels, with nitrate reductase genes of other filamentous fungi. Furthermore,
consensus regulatory signals thought to be involved in the control of nitrogen metabolism are present in the 5′ flanking region.
The cloned NIA1 gene has been used to develop a gene-transfer system based on nitrate assimilation. Stable nia1 mutants of S. nodorum defective in nitrate reductase were isolated by virtue of their resistance to chlorate. These were transformed back to nitrate
utilisation with the wild-type S. nodorum NIA1 gene. Southern analyses revealed that transformation occurred as a result of the integration of transforming DNA into the
fungal genome; in all cases examined, integration was targeted to the homologous sequence.
Received: 30 March / 9 June 1998 相似文献
42.
In a study of immunotherapy 41 children with seasonal rhinoconjunctivitis due to deciduous tree pollen allergy were monitored by means of symptom scoring, patient self-evaluation, conjunctival provocation tests and lymphocyte proliferation in vitro to the allergen. The lymphocyte responsiveness to birch pollen decreased significantly during the first year of immunotherapy. However, neither the lymphocyte responsiveness before treatment nor changes in lymphocyte reactivity during the immunotherapy correlated with the clinical efficacy of the therapy as evaluated by changes in symptom scores, self-evaluation or conjunctival provocation test changes in the individual patients. The results indicate the lymphocyte responsiveness to an allergen cannot be used to select patients for immunotherapy, i.e. to predict whether a patient would benefit from immunotherapy or not, or to evaluate the effects of immunotherapy after beginning the treatment. However, lymphocyte proliferation response to an allergen indicates clinical sensitivity. 相似文献
43.
Novitskii VV Naslednikova IO Urazova OI 《Bulletin of experimental biology and medicine》2003,136(4):344-347
Study of surface architectonics, blast transformation potential, and cytochemical activity of peripheral blood lymphocytes from children infected with Epstein-Barr virus revealed imbalance between structural, metabolic, and functional state of lymphocytes. This imbalance persists in delayed period after infection and determines long-term viral persistence in the macroorganism. 相似文献
44.
Lung carcinoma with sarcomatous transformation (LCST) is highly aggressive and characterized by local invasion and/or distant metastasis, which leads to a shorter survival than ordinary lung carcinomas. Therefore, to elucidate whether the malignant potential of the spindle cell element in LCST is associated with the alteration of the p53 gene, four cases were examined by analyses of overexpression of the p53 oncoprotein, mutation of the p53 gene and loss-of-heterozygosity (LOH) at chromosome 17p. In two cases overexpression of the p53 oncoprotein of the spindle cell component showed a higher degree of staining than that of the carcinoma component; LOH was identified in both carcinoma and sarcomatous components in one case, while in contrast, another case showed LOH in the sarcomatous component only. Mutations were clearly detected in two cases; one showed a CTT to CGT transversion in codon 194 of exon 6 in both components, whereas the other showed a CTG to CAG transversion in codon 265 of exon 8 in the sarcomatous component only. On the basis of these observations, it suggested that the sarcomatous component shows a higher frequency of p53 gene abnormalities in comparison to the carcinoma component. These results also suggested that the acquisition of malignant potential in the sarcomatous component, or the morphological alteration of carcinoma cells, is correlated with abnormalities associated with the p53 gene. 相似文献
45.
An episomal DNA vector (YpJA18), encoding two selectable recombinant yeast genes (TRP1, URA3), was constructed to assess the fidelity of DNA repair in haploid repair-competent (RAD) wild-type yeast and several radiation-sensitive mutants. Either a DNA double-strand break (DSB) or a double-strand gap of 169 bp (DSG) was introduced by restriction enzymes in-vitro within the coding sequence of the URA3 gene of this vector. To eliminate transfer artefacts, selection was first applied for the undamaged TRP1 gene followed by counter selection for URA3 gene activity, which indicated correct repair of the DSB and DSG. Correct repair of the damaged URA3 gene was found to be about 90% in RAD cells (normalized for the expression of undamaged URA3 in TRP
+ transformants). Plasmids isolated from the transformants (URA
+
TRP
+) carry both unique sites (ApaI and NcoI) within the URA3 gene indicating the precise restitution of the 169-bp gap. An excision-repair-defective rad4-4 mutant repaired these lesions as correctly as RAD cells, whereas the mutants rad50-1, rad51-1 and rad54-1, proven to be defective in DSB repair and mitotic recombination, showed less than 5% correct repair of such lesions. In contrast, a representative of the RAD6 epistasis group of genes, the rev2-1 mutant which is sensitive towards UV and ionizing radiation, had a significantly reduced ability (about 20%) for the correct repair of both DSBs and DSGs. 相似文献
46.
Ken Dewitte Marc Claeys Emeline Van Craenenbroeck Koen Monsieurs Hein Heidbuchel Vicky Hoymans Tibor Stoop 《Pathophysiology》2019,26(1):53-59
Aims
We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.Methods and results
In 20 healthy male volunteers (mean age 31?±?10 years), flow-mediated dilation (FMD) was measured before and after 20?min of arm ischaemia, followed by reperfusion. Remote ischaemic conditioning (RIC) was performed by applying 3 cycles of 5?min of ischaemia of the leg at the onset of index arm ischaemia. Each volunteer underwent the IR-induced vascular injury protocol with and without RIC in a crossover study design.In the control group, IR significantly reduced FMD (5.9?±?2.9% before IR vs. 2.2?±?3.7% after IR; p?<?0.001). This effect was significantly attenuated by performing RIC (FMD of 5.5?±?3.1% before IR vs. 4.0?±?3.4% % after IR; p for interaction?=?0.01). Serum levels of SOD and ADMA increased significantly whereas MCP-1 and VEGF levels decreased significantly.Only changes in SOD levels were significantly related to the degree of RIC induced protection (r²?=?0.34; p?=?0.018).Conclusion
RIC has protective effects against endothelial IR injury. Our biomarker study suggests that anti-oxidative stress mediators, such as SOD, seem to be more involved in the pathogenesis of RIC-induced protection in humans than angiogenesis factors or chemo-attractant cytokines. 相似文献47.
N Nandapalan C E Taylor J Greenwell M Scott R Scott E N Hey G L Toms 《Journal of medical virology》1986,20(1):79-87
We have recorded the systemic and mammary/mucosal immune responses of women following natural infection with RS virus during the second and third trimesters of pregnancy. Anti-RS virus IgG antibody levels in the sera of women collected in the first trimester of pregnancy showed a bimodal distribution with high and low antibody groups. Antibody levels increased after exposure to the winter RS virus epidemic in the second trimester of pregnancy, probably as a result of infection but only for women in the low antibody group. Despite the increases, antibody levels for these women remained well below those of the high antibody group. There was no rise in mean antibody levels after exposure in the third trimester, even among women with low antibody, suggesting a degree of immunosuppression in late pregnancy. There was no evidence that infection during pregnancy was associated with adverse consequences for the infant. Exposure to RS virus in the first two trimesters, but not the third, was associated with high colostral IgA antibody levels that were maintained in the milk throughout the first 7 weeks of lactation. There was a significant correlation between colostral and maternal nasal IgA antibody levels at delivery. Levels of blood or colostral lymphocyte transformation responses at delivery were unaffected by exposure to RS virus in pregnancy. These observations upon natural infection suggest that vaccination during pregnancy is likely to achieve only marginal effects upon serum antibody levels but boost maternal mammary/mucosal immunity. 相似文献
48.
Cochhobolus heterostrophus has alternate genes (MAT-1 andMAT-2) at its mating-type locus. Transformants of aMAT-1 or aMAT-2 strain carrying a transgene of opposite mating type can self and are dual maters; the transgene, however, promotes development of pseudothecia only, not ascospores. To determine if the resident gene interferes with the function of the transgene, transformation vectors were designed to delete different amounts (2.5 kb, 5.7 kb, and 6.3 kb) of DNA at theMAT locus. Deletions occurred at a higher frequency (about 90% of transformants) with linearized plasmid than with circular plasmid (about 15% of transformants), and all three vectors were equally efficient at gene replacement. BothMAT-1 andMAT-2 could be deleted with the same set of vectors. Re-transformation of deletion strains (regardless of deletion size) with a wild-type copy ofMAT restored full mating ability, indicating that the residentMAT gene interferes with function of theMAT transgene. Moreover, sexual development was normal whether theMAT transgene integrated at the homologous or at an ectopic site. 相似文献
49.
Summary
Agrobacterium tumefaciens naturally transfers DNA into plant cells and is clearly one of the most effective methods of directed DNA transfer presently available. Two kinds of vectors are commonly used. Cointegrative vectors have the foreign genes incorporated directly into the Ti plasmid. Binary vectors carry two plasmids; the main Ti plasmid where most of the T-DNA has been removed, and a second plasmid containing the foreign genes between the usual border sequences. The vir genes on the main plasmid function to mobilize the foreign genes into a plant cell. Most plant transformation methods follow the procedure of cocultivating wounded tissue with vir-gene-induced bacteria. The cocultivation step is followed by transfer to a selective medium containing antibiotics to kill the bacterium and to allow only growth of transformed tissue. Several selectable markers are available that include resistance to antibiotics, herbicides, or drugs. In addition, several scorable markers such as the bacterial glucuronidase, chloramphenicol acetyl transferase, and the Agrobacterium opine genes are used to verify transformation. Southern blotting and inheritance of transferred genes are ultimately used to demonstrate stable transformation. 相似文献
50.
Dr. W. Hofmann Th. Rommel Th. Schaupp F. Seuter J. A. Rossner F. M. Hecht G. Mall 《Virchows Archiv : an international journal of pathology》1980,385(2):151-168
Zusammenfassung In unserer ultrastrukturell durchgeführten Studie wurden Thromben in der Arteria carotis communis von Ratten nach einer zuerst von Meng und Seuter (1977) beschriebenen Methode experimentell erzeugt. Induktion der Thrombusbildung erfolgte in vivo durch Unterkühlung eines kleinen Gefäßabschnittes unter konstantem Druck und kurzfristiger Stase. Eine Änderung des Blutflusses wurde durch einen Silberclip erzeugt. Die geschädigten Gefäßsegmente einschließlich der Thromben bzw. deren Vorstufen wurden nach 5, 10, 30 min und 1, 4 und 24 h nach der Thrombosestimulation entnommen und fixiert. Semidünnschnitte und Ultradünnschnitte wurden im Licht- und Elektronenmikroskop morphologisch untersucht.Den Transformationsvorgängen im Thrombus konnten exakte Zeitmarken zugeordnet werden. Als wichtigstes histopathologisches Merkmal für die Altersbestimmung arterieller Thromben in der Frühphase der Thrombogenese werteten wir die Querstreifung der Fibrinfasern. Diese trat bereits nach 5 min auf, erreichte nach 30 min ein Maximum und verschwand als Folge der zunehmenden Verdichtung der Fasern nach einer Stunde. Nach 4 h sahen wir eine weitgehende Retraktion der Fibrinfasern, die nach 24 h zur Bildung des Fibrinfasergerüstes mit Einmauerung korpuskulärer Elemente führte. Überdies beobachteten wir zwei Thrombocytenaggregate von differenter Struktur. Wir unterschieden ein fibrinarmes Aggregat, in dem die Thrombocyten dichtgepackt und pseudopodienreich erschienen von einem thrombocytenarmen Aggregat mit reichlich interponierten Fibrinfasern. Die nach 5 min im Zentrum des Thrombus auftretende Agglutination der Plättchen im thrombocytenreichen Aggregat führte nach 30 min zur Thrombocytorrhexis und ergab daher einen weiteren Anhalt für die Altersbestimmung des Coagulum. Der entstandene celluläre Abraum stimulierte mononucleäre Zellen und Leukocyten zur Phagocytose. Daher sahen wir nach 4 h eine massive Leukocytose als Folge der frühen Thrombocytorrhexis. Nach 24 h war die viscöse Metamorphose im fibrinreichen und fibrinararmen Aggregat weitgehend abgeschlossen. Innerhalb des beobachteten Zeitraumes entstand eine Verballung und bizarre Deformierung der Erythrocyten, die bereits nach 5 min vom Zentrum des Thrombus ausging und nach 24 h die Peripherie erreichte. Eine Hämolyse der Erythrocyten war nach dieser Zeit noch nicht erkennbar.
Evolution in the early changes in the establishment of arterial thrombi
Summary Ultrastructural studies of thrombi were carried out on the common carotid artery of the rat using a method first described by Meng and Seuter (1977). Induction of thrombus formation in vivo was achieved by chilling of a small vessel segment under constant pressure and short-termed stasis. Disturbance of the blood flow was produced by a silver clip. The damaged vessel segments with the thrombotic deposits were removed 5, 10, 30 min, and 1, 4 and 24 h after stimulation of thrombosis. They were fixed and samples were studied as semithin and ultrathin sections morphologically using light and electronmicroscopy.In the maturation of thrombi exact time intervals could be determined. The most important histopathological characteristics for age determination of arterial thrombi in the early period of thrombogenesis were the cross stripes of fibrin fibres. They appeared after 5 min, reaching a maximum after 10 min and disappeared as a result of increasing fibre density after 1 h. After 4 h nearly complete retraction of fibrin fibres was found which led after 24 h to the formation of a corresponding frame walling in the corpuscular elements. Apart from this aggregation of thrombocytes, which were of two different types were observed, one showing a fibrin-poor aggregate in which the thrombocytes appeared densely packed with numerous pseudopods, and one showing a thrombocyte poor aggregate with abundant interposed fibrin fibres. Agglutination of platelets which occurred in the thrombocyte-rich aggregate in the centre of the thrombus after 5 min led to thrombocytorrhexis after 30 min. The resulting cellular waste stimulated phagocytosis by mononuclear cells and leucocytes. Because of this a massive leucocytosis was found as a result of the early thrombocytorrhexis after 4 h. After 24 h the viscous metamorphosis in the fibrin-rich and in the fibrin-poor aggregate was largely completed. Clumping and deformation of erythrocytes was observed in the middle of the thrombus after 5 min and at the periphery of the thrombus after 24 h. Haemolysis did not occur within this time interval.
Frau Antoni, Herrn Ing. grad. Derks und Herrn Rieger sei für ausgezeichnete technische Assistenz herzlichst gedankt. 相似文献